Kohan R03: Determining the mechanism for apoC-III stimulation of IL-10 and Tregs in the intestine: is this novel effect beneficial? Project Summary: Since the intestinal lymphatics are responsible for dietary fat transport and also serve as a main route for transport of antigens and antigen-presenting cells to the mesenteric lymph nodes, we hypothesized that intestinal apoC-III may also influence the intestinal immune system through its inhibition of dietary fat absorption. These studies will yield critical mechanistic information about the role of apoC-III in modulating T cells, and how this mediator of intestinal lipid absorption influences intestinal inflammatory disease. We will use T cell culture models, as well as in vivo studies in apoC-III transgenic mice, to determine how apoC-III alters T cell homeostasis and intestinal inflammation. Finally, due to the excitement about apoC-III in the cardiovascular field and as a pharmaceutical target, it is critical for us to determine how apoC-III is regulating the immune system.